Plain English Summary

Background and study aimsIt has been suggested that increased oxidative stress is an important cause of the impaired function of blood vessels in chronic kidney disease (CKD), but this has not been studied in detail. In this context, oxidative stress means an increased production of highly reactive oxygen molecules that have the potential to impair the function of blood vessels and the flow of blood to the kidneys. In this study, we are investigating whether infusing the antioxidant vitamin C, which can reduce oxidative stress, improves blood vessel function, and increases blood flow to the kidneys.Magnetic Resonance Imaging  or MRI  is a type of scan which allows us to get detailed pictures of internal organs. The advantage of this MRI is that it does not involve exposure to harmful radiation, and as far as we know, there are no long term health risks. We have developed a type of MRI scan called Arterial Spin Labelling (or ASL) that looks at the blood flow to the kidneys. This is a new technology which is not carried out in clinical practice at the moment. We hope that in the future it will allow us to look at the blood flow (or perfusion) to the kidneys in people with kidney disease or transplants without exposing them to harmful radiation. The purpose of this study is to if the results from the ASL-MRI correlate with markers of kidney function and oxidative stress, and if kidney blood flow is improved by vitamin C.

Who can participate?Three groups of people will be recruited. People with chronic kidney disease stages 3  5, people with vascular disease of the kidney, and people being assessed to act as a live kidney donor.

What does the study involve?For people with chronic kidney disease and vascular disease of the kidney: You will attend the Glasgow Cardiovascular Research Centre next to the Western Infirmary Glasgow having fasted for around 6 hours. After discussing what the study involves, you will be asked to sign a consent form. Your height, weight and blood pressures will be measured and a health questionnaire taken. An infusion of 100ml normal saline will be given and blood samples taken. The ASL-MRI scan will then be carried out. An infusion of vitamin C will then be given and further blood samples taken. A further ASL-MRI scan will then be carried out.For people acting as a live kidney donor: You will attend the Glasgow Cardiovascular Research Centre next to the Western Infirmary Glasgow after having fasted for around 6 hours. After discussing what the study involves, you will be asked to sign a consent form. Your height, weight and blood pressures will be measured and a health questionnaire taken. Samples of blood and urine will be taken. The ASL-MRI scan will then be carried out.

What are the possible benefits and risks of participating?There are no direct benefits to the participants, however the study may result in treatment which will improve cardiovascular function in people with kidney impairment, and help to develop new types of imaging which will be useful in people with kidney disease.The risks for people with chronic kidney disease and kidney vascular disease are as follows: We will take blood and urine samples to ensure that your kidneys are working normally and that there is no sign of any other health problem of which you are unaware. We will take a small amount of blood from the vein in your arm which in some rare cases can result in minor bruising. The amount of blood taken does not pose any risks. A blood pressure cuff can cause discomfort for the very brief period of time it is inflated, and in extremely rare cases cause a bruise. Some studies have suggested that administration of vitamin C may cause kidney stones. To minimize any such risk, you should not take part in this study if you previously had a kidney stone or if you are already taking daily vitamin C supplements.The risks for people acting as live kidney donors are as follows: We will take blood and urine samples to ensure that your kidneys are working normally and that there is no sign of any other health problem of which you are unaware. We will take a small amount of blood from the vein in your arm which in some rare cases can result in minor bruising. The amount of blood taken does not pose any risks. A blood pressure cuff can cause discomfort for the very brief period of time it is inflated, and in extremely rare cases cause a bruise.

Where is the study run from?The British Heart Foundation Glasgow Cardiovascular Research Centre (UK).

When is study starting and how long is it expected to run for?The study starts in August 2013 and is expected to run until February 2015. Each individual participant undergoes only one study visit, and will not be followed up after this.

Who is funding the study?NHS Greater Glasgow and Clyde Renal Unit Endowment Fund and Darlindas Charity for Renal Research (UK).

Who is the main contact?Dr Keith Gillis, Clinical Research Fellowkeithgillis@nhs.net

Study design

Primary study design

Secondary study design

Trial setting

Trial type

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Renal, Kidney perfusion, Magnetic resonance imaging

Intervention

Participants are given ascorbic acid 2000mg in 100ml 0.9% saline given intravenously by peripheral cannula over 10 minutes. There is no randomisation and follow up is for the duration of the study visit, that is around 1.5 hours.

Intervention type

Supplement

Phase

Not Applicable

Drug names

Vitamin C

Primary outcome measure

Change in renal perfusion by ASL MRI, measured after saline and then after ascorbic acid

Secondary outcome measures

Biomarkers of oxidative stress both measured after saline and then after ascorbic acid1. Total antioxidant capacity measured by colorimetric assay2. Rate of reactive oxygen species generation measured by electron paramagnetic resonance

Overall trial start date

05/07/2013

Overall trial end date

01/02/2015

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged over 18 years2. Written informed consent3. CKD - people with chronic kidney disease stages 3 - 5, with an eGFR 15-30ml/min4. LKD - people being assessed to act as live kidney donors5. RVD - people with renovascular disease documented on imaging and after assessment by a nephrologist

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

36

Participant exclusion criteria

1. Known liver disease (alcoholic liver disease, hepatitis, cirrhosis)2. Known HIV infection3. Known recreational drug or alcohol abuse4. Clinical signs of acute infection5. Known pregnancy6. Women of childbearing age are who are at risk of pregnancy7. Metal prosthesis contraindicating MRI8. Claustrophobia contraindicating MRI